Pharmacological and Toxicological Threshold of Bisammonium Tetrakis 4-(N,N-Dimethylamino)pyridinium Decavanadate in a Rat Model of Metabolic Syndrome and Insulin Resistance
Joint Authors
Brambila, Eduardo
Treviño, Samuel
Diaz-Fonseca, Alfonso
Flores-Hernandez, José Ángel
González-Vergara, Enrique
Sánchez-Lara, Eduardo
Sarmiento-Ortega, Víctor Enrique
Meléndez, Francisco J.
Source
Bioinorganic Chemistry and Applications
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-06-19
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Vanadium(IV/V) compounds have been studied as possible metallopharmaceutical drugs against diabetes mellitus.
However, mechanisms of action and toxicological threshold have been tackled poorly so far.
In this paper, our purposes were to evaluate the metabolic activity on dyslipidemia and dysglycemia, insulin signaling in liver and adipose tissue, and toxicology of the title compound.
To do so, the previously reported bisammonium tetrakis 4-(N,N-dimethylamino)pyridinium decavanadate, the formula of which is [DMAPH]4(NH4)2[V10O28]·8H2O (where DMAPH is 4-dimethylaminopyridinium ion), was synthesized, and its dose-response curve on hyperglycemic rats was evaluated.
A Long–Evans rat model showing dyslipidemia and dysglycemia with parameters that reproduce metabolic syndrome and severe insulin resistance was generated.
Two different dosages, 5 µmol and 10 µmol twice a week of the title compound (equivalent to 2.43 mg·V/kg/day and 4.86 mg·V/kg/day, resp.), were administered intraperitoneal (i.p.) for two months.
Then, an improvement on each of the following parameters was observed at a 5 µmol dose: weight reduction, abdominal perimeter, fatty index, body mass index, oral glucose tolerance test, lipid profile, and adipokine and insulin resistance indexes.
Nevertheless, when the toxicological profile was evaluated at a 10 µmol dose, it did not show complete improvement, tested by the liver and adipose histology, as well as by insulin receptor phosphorylation and GLUT-4 expression.
In conclusion, the title compound administration produces regulation on lipids and carbohydrates, regardless of dose, but the pharmacological and toxicological threshold for cell regulation are suggested to be up to 5 µmol (2.43 mg·V/kg/day) dose twice per week.
American Psychological Association (APA)
Treviño, Samuel& Diaz-Fonseca, Alfonso& Sánchez-Lara, Eduardo& Sarmiento-Ortega, Víctor Enrique& Flores-Hernandez, José Ángel& Brambila, Eduardo…[et al.]. 2018. Pharmacological and Toxicological Threshold of Bisammonium Tetrakis 4-(N,N-Dimethylamino)pyridinium Decavanadate in a Rat Model of Metabolic Syndrome and Insulin Resistance. Bioinorganic Chemistry and Applications،Vol. 2018, no. 2018, pp.1-13.
https://search.emarefa.net/detail/BIM-1123091
Modern Language Association (MLA)
Treviño, Samuel…[et al.]. Pharmacological and Toxicological Threshold of Bisammonium Tetrakis 4-(N,N-Dimethylamino)pyridinium Decavanadate in a Rat Model of Metabolic Syndrome and Insulin Resistance. Bioinorganic Chemistry and Applications No. 2018 (2018), pp.1-13.
https://search.emarefa.net/detail/BIM-1123091
American Medical Association (AMA)
Treviño, Samuel& Diaz-Fonseca, Alfonso& Sánchez-Lara, Eduardo& Sarmiento-Ortega, Víctor Enrique& Flores-Hernandez, José Ángel& Brambila, Eduardo…[et al.]. Pharmacological and Toxicological Threshold of Bisammonium Tetrakis 4-(N,N-Dimethylamino)pyridinium Decavanadate in a Rat Model of Metabolic Syndrome and Insulin Resistance. Bioinorganic Chemistry and Applications. 2018. Vol. 2018, no. 2018, pp.1-13.
https://search.emarefa.net/detail/BIM-1123091
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1123091